Literature Scan

placebo-controlled trial , researchers enrolled 230 patients who were ≥5 years old , had experienced two or more pain crises within the previous year , and were receiving hydroxyurea at a stable dose for at least three months prior to enrollment .

The researchers randomized patients 2:1 to receive either :

• pharmaceutical-grade L-glutamine powder ( n = 152 )

• placebo powder ( n = 78 ) start ], with sustained separation of curves over the duration of the trial ,” the authors noted .

However , no differences were observed between either group in the number of visits to the emergency department that did not result in hospitalization ( p = 0.09 ).

All-grade adverse events ( AEs ) and serious AEs occurred more frequently in the placebo group than the L-glutamine group ( 100 % vs . 98 % and

TABLE 2 . Endpoint Analysis at 48 Weeks

L-glutamine ( n = 152 )

Placebo ( n = 78 ) p Value

Patients received L-glutamine powder 0.3 g / kg twice daily for a total of 48 weeks . Therapy was then tapered for three weeks , followed by a two-week observation period , for a total trial duration of 53 weeks .

The primary efficacy endpoint was the number of pain crises during the 48-week treatment period . For the purposes of their study , the researchers defined a pain crisis as any pain resulting in treatment with parenterally administered narcotic or ketorolac therapy in the emergency department , in an outpatient treatment center , or during hospitalization .

Secondary efficacy endpoints included the number of hospital admissions for sickle cell – related pain , hematologic changes ( including hemoglobin and hematocrit levels and reticulocyte count ) from baseline to 48 weeks , and the number of visits to the emergency department or outpatient treatment center for sickle cell – related pain .

During the 48-week trial period , patients in the L-glutamine group experienced significantly fewer pain crises compared with those in the placebo group ( median = 3 [ range = 0-15 ] vs . 4 [ range = 0-15 ]; p = 0.005 ). This translated to a 25-percent reduction in the number of sickle cell – related pain crises , compared with placebo , during the 48-week treatment period .

L-glutamine also was associated with a lower median number of hospitalizations for sickle cell – related pain and other secondary endpoints ( TABLE 2 ).

Participants treated with L-glutamine had a longer time to first pain crisis and a longer time between first and second pain crises , compared with those treated with placebo :

• median number of days to first pain crisis : 84 ( range = 62-109 days ) vs . 54 ( range = 31-73 days ; p = 0.02 )

• median number of days to second pain crisis : 212 ( range = 153-250 days ) vs . 133 ( range = 115-179 days ; p = 0.03 )

“ The time to the first pain crisis began to diverge within two weeks [ of treatment

BESPONSA™ ( inotuzumab ozogamicin ) is indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia ( ALL )

Deep remission refers to MRD-negative remission , defined in the INO-VATE ALL study as leukemic cells comprising < 1 x 10 -4 of bone marrow nucleated cells per flow cytometry . 1

IMPORTANT SAFETY INFORMATION

WARNING : HEPATOTOXICITY , INCLUDING HEPATIC VENO-OCCLUSIVE DISEASE ( VOD ) ( ALSO KNOWN AS SINUSOIDAL OBSTRUCTION SYNDROME ) and INCREASED RISK OF POST – HEMATOPOIETIC STEM CELL TRANSPLANT ( HSCT ) NON-RELAPSE MORTALITY ( NRM ):

• Hepatotoxicity , including fatal and life-threatening VOD , occurred in patients who received BESPONSA . The risk of VOD was greater in patients who underwent HSCT after BESPONSA treatment . The use of HSCT conditioning regimens containing 2 alkylating agents and last total bilirubin ≥ upper limit of normal ( ULN ) before HSCT were significantly associated with an increased risk of VOD

• Other risk factors for VOD in patients treated with BESPONSA included ongoing or prior liver disease , prior HSCT , increased age , later salvage lines , and a greater number of BESPONSA treatment cycles

• Elevation of liver tests may require dosing interruption , dose reduction , or permanent discontinuation of BESPONSA . Permanently discontinue treatment if VOD occurs . If severe VOD occurs , treat according to standard medical practice

• There was a higher post-HSCT non-relapse mortality rate in patients receiving BESPONSA , resulting in a higher Day 100 post-HSCT mortality rate

Hepatotoxicity , Including Hepatic VOD : Hepatotoxicity , including fatal and life-threatening VOD , occurred in 23 / 164 patients ( 14 %) during or following treatment with BESPONSA or following subsequent HSCT . VOD was reported up to 56 days after the last dose during treatment or follow-up without an intervening HSCT . The median time from HSCT to onset of VOD was 15 days .

Patients with prior VOD or serious ongoing liver disease are at an increased risk of worsening liver disease , including development of VOD , following

The efficacy of BESPONSA was established on the basis of CR ( 35.8 % [ 39 / 109 ; 95 % CI , 26.8-45.5 ] with BESPONSA vs 17.4 % [ 19 / 109 ; 95 % CI , 10.8-25.9 ] with SC ), the duration of CR ( 8.0 months [ 95 % CI , 4.9-10.4 ] with BESPONSA vs 4.9 months [ 95 % CI , 2.9-7.2 ] with SC ), and the proportion of MRD-negative CR ( 89.7 % [ 35 / 39 ; 95 % CI , 75.8-97.1 ] with BESPONSA vs 31.6 % [ 6 / 19 ; 95 % CI , 12.6-56.6 ] with SC ) in the first 218 randomized patients . 1

treatment with BESPONSA . Monitor closely for signs and symptoms of VOD ; these may include elevations in total bilirubin , hepatomegaly ( which may be painful ), rapid weight gain , and ascites . For patients proceeding to HSCT , the recommended duration of treatment with BESPONSA is 2 cycles . A third cycle may be considered for patients who do not achieve a CR or CRi and MRD-negativity after 2 cycles . Monitor liver tests closely during the first month post HSCT , then less frequently thereafter , according to standard medical practice .

Grade 3 / 4 increases in aspartate aminotransferase , alanine aminotransferase , and total bilirubin occurred in 7 / 160 ( 4 %), 7 / 161 ( 4 %), and 8 / 161 ( 5 %) patients , respectively .

Increased Risk of Post-HSCT Non-Relapse Mortality ( NRM ): There was a higher post-HSCT NRM rate in patients receiving BESPONSA , resulting in a higher Day 100 post-HSCT mortality rate . The rate of post-HSCT NRM was 31 / 79 ( 39 %) with BESPONSA and 8 / 35 ( 23 %) with investigator ’ s choice of chemotherapy . In the BESPONSA arm , the most common causes of post- HSCT NRM included VOD and infections . Monitor closely for toxicities post HSCT , including signs and symptoms of infection and VOD .

Myelosuppression : Myelosuppression , and severe , life-threatening , and fatal complications of myelosuppression , including hemorrhagic events and infections , have occurred with BESPONSA . Thrombocytopenia and neutropenia were reported in 83 / 164 patients ( 51 %) and 81 / 164 patients ( 49 %), respectively . Febrile neutropenia was reported in 43 / 164 patients ( 26 %).

Monitor complete blood counts prior to each dose of BESPONSA and monitor for signs and symptoms of infection , bleeding / hemorrhage , or other effects of myelosuppression during treatment and provide appropriate management . As appropriate , administer prophylactic anti-infectives during and after treatment with BESPONSA . Dose interruption , dose reduction , or permanent discontinuation may be required .

22 ASH Clinical News